Hyperkalemia and renal function during monotherapy and dual renin-angiotensin blockade in the community setting

Daniel Kurnik*, Janet Vesterman-Landes, Martin Bialik, Itzhak Katzir, Yosef Lomnicky, Hillel Halkin, Ronen Loebstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: In controlled trials, dual therapy with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) is associated with hyperkalemia and decreased renal function, but there is no information about these adverse effects in clinical practice. Objective: The aim of this study was to assess the incidence of hyperkalemia and decreased renal function during dual therapy (ACE-I plus ARB) in a community-based setting. Methods: In a retrospective cohort database study, we identified patients who received ARBs added to ongoing ACE-I therapy and who had at least 1 measurement of serum creatinine and potassium during each treatment period. We compared rates of hyperkalemia (>5.5 mmol/L) during equal periods of monotherapy and dual therapy and the rate of a significant rise in serum creatinine (≥0.5 mg/dL) between study periods. We assessed the impact of potential confounders on outcomes by logistic regression analysis. Results: Among 425 patients (median follow-up 19 months for each treatment period), hyperkalemia was 2-fold more common during dual therapy than monotherapy (11.1% and 5.6% of patients, respectively) (relative risk = 1.96; 95% CI, 1.22-3.14; P < 0.001). In 77 patients with reduced renal function on monotherapy (serum creatinine ≥1.5 mg/dL), the rate of hyperkalemia was 20.8/100 patient-years, resulting in a number needed to harm of 10.1 patients, compared with 52.6 patients among those with preserved renal function. Mean serum creatinine between treatment periods increased >0.5 mg/dL in 7.5% of patients, more commonly in patients with decreased (18.2%) than with preserved (5.2%) baseline renal function (P < 0.001). Conclusion: In the community setting, dual therapy was associated with hyperkalemia and a decrease in renal function. The absolute risks were especially high among patients with reduced baseline renal function.

Original languageEnglish
Pages (from-to)456-464
Number of pages9
JournalClinical Therapeutics
Issue number4
StatePublished - Apr 2011


  • Adverse drug reaction
  • Angiotensin converting enzyme inhibitors
  • Angiotensin receptor blockers
  • Pharmacoepidemiology


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